P-095: PARTNERSHIP WITH AFRICAN INVESTIGATOR SITES TO INCREASE RECRUITMENT IN CLINICAL TRIALS: EXPERIENCE FROM SIKAMIC TRIAL
Authors: BARTOLUCCI P., DIOP S., GUINDO A., ARLET J., CANNAS G.
Journal: HemaSphere (2022)

Purpose: Sickle cell disease (SCD) is associated with a high frequency of chronic kidney disease (CKD), which constitutes an independent risk factor for death in this population. In term of epidemiology SCD-associated nephropathy (SCAN) is a growing matter of concern because chronic renal failure affects from 12% to 16% of adult patients1-3. Thus, the early diagnosis of SCAN together with the recognition of the associated clinical and biologic risk factors are of major interest to make it possible to initiate kidney-protective therapy at early stages of renal impairment and to impact the outcome of the disease. Albuminuria is a relevant biomarker for the detection of early glomerular damage in patients with SCD. Several observational studies, especially in the adult population, have provided evidence that hydroxycarbamide (HU)would be beneficial in SCD patients with impaired glomerular function4-5 1.Falk RJ, Scheinman J, Phillips G, et al. Prevalence and pathologic features of sickle cell nephropathy and response to inhibition of angiotensin-converting enzyme. N Engl J Med. 1992 Apr 2;326(14):910-5. 2.Powars DR, Chan LS, Hiti A, Ramicone E, Johnson C. Outcome of sickle cell anemia: a 4-decade observational study of 1056 patients. Medicine (Baltimore). 2005 Nov;84(6):363-76. 3.Yeruva SL, Paul Y, Oneal P, Nouraie M. Renal Failure in Sickle Cell Disease: Prevalence, Predictors of Disease, Mortality and Effect on Length of Hospital Stay. Hemoglobin. 2016 Sep;40(5):295-9. 4.Bartolucci P, Habibi A, Stehle T, et al. Six Months of Hydroxyurea Reduces Albuminuria in Patients with Sickle Cell Disease. J Am Soc Nephrol. 2015 Nov 19. Eng. 5.Laurin LP, Nachman PH, Desai PC, Ataga KI, Derebail VK. Hydroxyurea is associated with lower prevalence of albuminuria in adults with sickle cell disease. Nephrol Dial Transplant. 2014 Jun;29(6):1211-8. Materials and methods: The SIKAMIC trial evaluates the effect of six-month of hydroxycarbamide compared to placebo on albuminuria. It is a Phase-IIb, international, multicentric, randomized, double blind placebo-controlled trial in adult patients with HbSS or HbSβ0 SCD and ACR between 3 and 100 mg/mmol. Results: Initially it was planned to enroll 120 patients (60 patients for each study group) in 21 French centres. The recruitment started in August 2019 but1,5 years later only 9 patients were randomized. Because most of the patients with renal impairment in France were often treated with HU or converting-enzyme inhibitors which was not the case in Africa. Consequently 3 African centres were selected to participate in the study. Conclusion: Important points must be considered when extension to Africa is planned: Regulatory processes are longer than in Europe, Support with local CRO experimented in the conduct of trials in Africa is recommended, Local features such as unavailability of some exams, long distance from home to clinical centre, more dedicated time for information of patients must be managed in term of finance and training.In Sikamic trial, from the submission of amendment at the end of 2020 to the recruitment of the first African patient nine months were required. On March 2022, 28 patients were randomized (20 in France, 8 in Africa). The recruitment is still ongoing. The authors do not declare any conflict of interest